This project is designed to study immune responses and consequent allergic reactions by inhalation to experimental animals. Immunogenic requirements for the development of systemic and local, humoral and cell-mediated immunologic reactions will be determined using soluble and particulate antigens with and without adjuvants. We have previously demonstrated the occurrence of hypersensitivity reactions in the lungs of animals selectively sensitized systemically, if such animals are challenged with aerosolized antigen in acute experiments. Chronic or repeated inhalational challenge is more akin to human correlates, but with repeated challenge locally the immune responses of the animal are modified. We therefore propose to study histopathological changes produced by chronic inhalational challenge with antigen pari passu with developing immunogenic responses. In this way, we hope to better understand immunogenic requirements and pathogenesis in various human lung diseases resulting from inhalation of antigen.